Actos Now for Prevention of Diabetes (ACT NOW)

Condition(s) targeted: Impaired Glucose Tolerance; Type 2 Diabetes

Intervention: Pioglitazone (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Texas Diabetes Institute

Official(s) and/or principal investigator(s):
Ralph A. DeFronzo, M.D., Principal Investigator, Affiliation: Texas Diabetes Institute

The purpose of this study is to examine whether pioglitazone versus placebo can reduce the conversion rate of impaired glucose tolerance (IGT) to type 2 diabetes mellitus

Official title: Actos Now for Prevention of Diabetes (ACT NOW)

Study design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Prevention of Type 2 Diabetes

Secondary outcome:

Improvement in glycemic control

Change in insulin secretion

Change in insulin sensitivity

Improvement in cardiovascular risk factors

Change in blood pressure

Change in atherosclerosis

Occurrence of cardiovascular morbidity and mortality

Change in body composition

Change in adipocytokines

Change in plasma sex steroids

Change in renal function

Adverse events

Detailed description: IGT is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, the hyperglycemia-related complications of this devastating disease can be prevented. Subjects with IGT will be identified with an oral glucose tolerance test (OGTT). Eligible subjects also will have a measurement of first phase insulin secretion and insulin sensitivity using the frequently sampled intravenous glucose tolerance test (FSIVGTT) and carotid intimal media thickness using carotid ultrasound. Following these measurements subjects will be randomized to receive pioglitazone or placebo and they will return every 3 months for determination of fasting plasma glucose (FPG) concentration and interim medical history. Recruitment will take place over 15 months. From the time that the recruitment period ends, subjects will be followed for a total of 24 months on pioglitazone or placebo. The OGTT will be repeated at 15,27, and 39 months, or if the FPG is ≥ 126 mg/dl on the 3-month follow up visits. If the diagnosis of diabetes is established before month 39 or at month 39, the FSIVGTT and carotid ultrasound will be repeated. At 39 months, subjects will be washed out of pioglitazone or placebo and the OGTT, FSIVGTT, and carotid ultrasound will be repeated at month 45.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Men and women

- All ethnic groups

- 18 years of age and older

- Impaired glucose tolerance by glucose tolerance test (fasting glucose 95-125 mg/dl and

2 hr glucose of 140-199 mg/dl)

- At least one of the following:

- One or more components of the insulin resistance syndrome (HDL < 40 mg/dl in

females and <35 mg/dl in males, fasting triglycerides > 150 mg/dl, blood pressure > 135/85 mmHg, BMI > 24 kg/m2, waist circumference > 102 cm in men and > 88 cm in women)

- One or more first degree relatives with type 2 diabetes

- History of gestational diabetes

- Polycystic ovarian disease

- Minority ethnic background (Mexican American, African American, Asian and Pacific

Islanders, Native American)

Exclusion Criteria:

- Type 2 diabetes

- Previously treated with thiazolidinediones (ever) or metformin (within one year)

- Previously treated with a sulfonylurea, a meglitinide, an alpha glucosidase inhibitor

for more than a week within last year or within the 3 months prior to randomization

- Previously treated with insulin (other than during pregnancy) for more than one week

within the last year or within the 3 months prior to randomization

- Cardiovascular disease

- Hospitalization for treatment of heart disease or stroke in past 6 months

- New York Heart Association Functional Class > 2

- Left bundle branch block or third degree AV block

- Aortic stenosis

- SBP > 180 mmHg or DBP > 105 mmHg

- Renal disease

- Anemia

- Hepatitis

- GI diseases (pancreatitis, inflammatory bowel disease)

- Recent or significant abdominal surgery

- Advanced pulmonary disease

- Chronic infections

- Weight loss > 10% in past 6 months

- Pregnancy and childbearing

- Major psychiatric disorders

- Excessive alcohol intake

- Thiazide use > 25 mg per day

- Non-selective beta blockers

- Niacin

- Systemic glucocorticoids

- Weight loss or weight gain medication

- Thyroid disease-suboptimally treated

- Active endocrine diseases (Cushing's, acromegaly)

- Plasma triglycerides over 400 mg/dl (despite treatment)

- History bladder cancer

- Hematuria

Carl T. Hayden VA Medical Center, Phoenix, Arizona 85012, United States

USC-Keck School of Medicine, Los Angeles, California 90033, United States

University of California San Diego-San Diego VA Medical Center, San Diego, California 92161, United States

Georgetown University, Washington, District of Columbia 20007, United States

Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, United States

SUNY Health Science Center, Brooklyn, New York 11203, United States

University of Tennessee, Memphis, Tennessee 38163, United States

Texas Diabetes Institute, San Antonio, Texas 78207, United States

American Diabetes Association

Starting date: January 2004
Ending date: May 2007
Last updated: February 16, 2006